Quantitative characteristics of calcitonin-producing cells in the thyroid and lungs of uremic rats.

Uremia leads to a number of metabolic and hormonal disorders induced by renal failure with definite biological and clinical sequels. For this reason and the absence of reports on influence of CRF on calcitonin (CT)-producing cells of the thyroid glands and airways, the author decided to investigate the behavior of neuroendocrine cells in experimental uremia, taking CT-producing cells as an example. The aim of the present study was to examine the number and distribution of CT-producing cells in the thyroid glands and lungs of uremic rats. Fragments of the thyroids and lungs were collected one week after nephrectomy. Paraffin-embedded sections were stained with H+E and by silver impregnation. To identify neuroendocrine cells, immunohistochemical reaction was performed with the use of a specific antibody against calcitonin. It was revealed that the number of CT-immunoreactive cells decrease in the thyroid and considerable increase in the lungs of rats, when compared to the value in the control animals. The results can be regarded as the morphological manifestation of calcitonin-producing endocrine cells in the rat thyroid and lungs to disorders in the internal environment of the body induced by the impairment of renal parenchyma functioning

Ghrelin-immunoreactive cells in the gastrointestinal tract of hypertensive rats

Introduction. Ghrelin, an appetite-stimulating hormone secreted by the endocrine cells of the gastrointestinal (GI) tract, has recently been shown to affect the function of the cardiovascular system. This study aimed to assess the number and morphology of ghrelin-immunopositive (GhrIP) cells in the gastrointestinal tract of rats at different developmental phases of experimentally evoked renovascular hypertension. Material and methods. The study involved 40 rats divided into two groups: control (C; n = 20) and rats with experimentally induced hypertension (EH; n = 20). The Goldblatt model of two-kidneys, one clip (2K1C) was used to induce hypertension. Renovascular hypertension was maintained for either 3 (EH1 group; n = 10) or 42 (EH2 group; n = 10) days. Paraffin sections from the cardia, corpus and pylorus of the stomach, as well as from the duodenum, jejunum, ileum and colon were processed for peroxidase immunohistochemistry. Results. The number of GhrIP cells was significantly higher in the cardia and corpus of the stomach as well as the duodenum and jejunum of hypertensive rats compared to that found in the control animals. Conclusions. The increased number of GhrIP cells in the rat gastrointestinal tract after partial unilateral ligation of the renal artery suggests that renovascular hypertension may affect ghrelin secretion, which can contribute to the development of cardiovascular complications

Caspase-3 as an important factor in the early cytotoxic effect of nickel on oral mucosa cells in patients treated orthodontically

Introduction. The effect of fixed orthodontic appliances on biochemical changes in saliva and pathophysiological status of the oral cavity is not clear. Recent data showed that nickel (Ni) released from orthodontic appliances can decrease cellular viability, induce DNA damage and apoptosis in oral mucosa cells. Since the mechanism of these Ni effects is unknown, the aim of our study was to analyze the expression of caspase-3 in epithelial cells of oral mucosa in healthy individuals treated orthodontically. Material and methods. Twenty-eight volunteers participated in the study. Epithelial cells were collected from oral mucosa directly before appliance insertion, one week after the insertion, and 24 four weeks after the insertion of fixed appliances. Cellular identification and measurements were conducted by light microscopy. Caspase-3 expression was evaluated immunochemically. Nickel concentration in saliva was also determined. Results. A significantly higher number of oral epithelial cells with caspase-3 immunoreactivity in was found one week, but not 24 weeks, after orthodontic treatment. The enhanced expression of caspase-3 was accompanied by increased nickel concentration in saliva. Conclusions. Our data suggests that nickel released from orthodontic appliances can activate caspase-3 and this mechanism may be partially responsible for the cytotoxic action of nickel in the oral cavity of orthodontically-treated individuals

Effects of CP 55,940 — agonist of CB1 cannabinoid receptors on ghrelin and somatostatin producing cells in the rat pancreas

Cannabinoids participate in the modulation of numerous functions in the human organism, increasing the sense of hunger, affecting carbohydrate and lipid metabolism, and controlling systemic energy balance mechanisms. Moreover, they influence the endocrine system functions, acting via two types of receptors, CB1 and CB2. The aim of the present study was to examine the number, distribution and activity of ghrelin and somatostatin producing endocrine cells in the pancreas of rats after a single administration of selective CP 55,940 agonist of CB1 receptor. The study was performed on 20 rats. Neuroendocrine cells were identified by immunohistochemical reactions, involving specific antibodies against ghrelin and somatostatin. The distribution and number of ghrelin- and somatostatin-immunoreactive cells were separately studied in five pancreas islets of each section. A performed analysis showed a decreased number of somatostatin-immunoreactive cells and a weak immunoreactivity of ghrelin and somatostatin containing neuroendocrine cells in the pancreatic islets of experimental rats, compared to control animals. The obtained results suggest that a single administration of a selective CP 55,940 agonist of CB1 receptor influences the immunoreactivity of endocrine cells with ghrelin and somatostatin expression in the pancreas islets

Preliminary comparative immunocytochemical study of respiratory tract endocrine cells in certain rodents

Studies were performed on 3 species belonging to two families: Microtidae (7 common voles and 7 pine voles), and Muridae - 10 Wistar rats. In rodents the airways endocrine cells (ECs) are localised in the epithelium lining the larynx, trachea, bronchi, bronchioles and lung. CGRP-, synaptophysin (SY)-, calcitonin (CT)-, neuron-specific enolase (NSE)- and chromogranin A (CA)- immunoreactivity were nearly totally co-localised in ECs. In the region of the tracheo-larynx junction, CGRP- and NSE-positive cells were observed in the epithelium of the glands. It is surmised that some of the CGRP-positive ECs do not generate CT and CA, for the most part in ECs. In Microtidae ECs were more abundant than in the rat and were found even in the epithelium lining of the inside larynx in the transition region before the trachea

The activity of gastric ghrelin positive cells in obese patients treated surgically.

Ghrelin is a 28 amino acid peptide hormone regulating food intake and stimulating releasement of growth hormone. It is produced in a distinct endocrine call known as X/A - like cells. The most abundant source of this very important factor in energy homeostasis is gastric fundus. Regulatory mechanisms of ghrelin synthesis and secretion in physiological and pathological states are not discovered completely. The aim of our study was evaluation of the activity of gastric X/A-like cells in obese patients before and after the most popular surgical bariatric procedures - Roux - Y Gastric Bypass (RYGB) and Laparoscopic Adjustable Gastric Banding (LAGB). Obese patients in number 18 took part in the study. LAGB was performed in 7 patients and RYGB in 11 patients. Peripheral blood was taken from each patient before operation and first day, seventh day, one month and three months after surgery. Ghrelin level was determined by RIA technique. The specimen of stomach was taken from circular stapler after gastrojejunostomy during RYGB and immunohistochemical study of gastric mucosa, using the EnVision method and specific monoclonal antybodies against ghrelin was performed. The intensity of ghrelin-immunoreactivity in X/A-like cells was analyzed using Olympus Cell D image analysis system. Efficiency of bariatric procedures was estimated by EWL- excess weight loss. We observed very strong immunohistochemical reactions of gastric X/A-like cells, accompanied by lower ghrelin plasma concentration, in comparison to the control group. LAGB procedure induced increase of ghrelin plasma level while RYGB procedure induced decrease of this hormone. The main finding of the present study is the hypoactivity of gastric X/A-like cells in obese patients in comparison to the control group

Cytology of nasal mucosa, olfactometry and rhinomanometry in patients after CO2 laser mucotomy in inferior turbinate hypertrophy.

To evaluate the cytology of nasal mucosa and sense of smell and nasal patency in patients underwent carbon dioxide laser turbinoplasty (CO2 laser mucotomy) due to chronic nasal hypertrophy. 46 patients with inferior turbinate hypertrophy underwent complete laryngological examination, anterior rhinomanometry, olfactory measurements and cytology of nasal mucous which were performed before and 3 months after CO2 laser mucotomy. Laser mucotomy was performed under local anesthesia. Cytograms revealed significant changes in cell proportion before and after the surgery. Goblet cells predominated in nasal smears before the laser mucotomy. An average percentage of eosinophils in evaluated cytograms before the surgery was 2.1%. Three months after laser mucotomy we observed decrease in goblet cells proportion (the mean range of goblet cells was 16.4%) in nasal cytology. We have also observed improvement in olfactory function, however only in 7 patients (20.6%). The mean value of total nasal airway resistance (NAR) before treatment was 0.98+/-0.24 Pa/cm3/s at 75 Pa. Rhinomanometry after 3 months showed a reduction in mean total resistance from the pretreatment level to 0.77 Pa/cm3/s. We believe that CO2 laser mucotomy is an efficacious, minimally invasive and easy to use treatment of inferior turbinate hypertrophy which is performed under local anesthesia with little discomfort for the patient and does not require hospitalization

The concentration of kynurenine in rat model of asthma.

Asthma is a chronic inflammatory disease that involves the immune system activation. Evidence is accumulating about the role of kynurenine pathway in the immune system regulation. The kynurenine pathway includes several metabolites of tryptophan, among others kynurenine (KYN). To study the immunological system regulation in asthma a simple and sensitive models of asthma are required. In the present study we induced rat model of asthma using ovalbumin (OVA) sensitization followed by challenge with OVA. The development of asthma has been confirmed by plasma total IgE measurement and the histological examination. The concentration of KYN has been determined in plasma, lungs and liver by high-performance liquid chromatography (HPLC). In OVA sensitized rats the concentration of total IgE was statistically significantly increased as compared to VEH sensitized control groups (437.6 +/- 97.7 kU/l vs 159.2 +/- 22.7 kU/l, respectively; p< 0.01). In asthmatic animals, the number of eosinophils, neutrophils and mast cells increased considerably, and epithelial lesion and the increase in airway epithelium goblet cells and edema of bronchial mucosa were present. We did not observe any significant changes in the concentration of KYN in plasma, lungs or liver between studied groups. In conclusion, the concentration of KYN remains unchanged in asthmatic animals as compared to control groups. Further studies using rat model of asthma are warranted to establish the role of kynurenine pathway regulation in asthma

The toxicokinetic profile of Dex40-GTMAC3 : a novel polysaccharide candidate for reversal of unfractionated heparin

Though protamine sulfate is the only approved antidote of unfractionated heparin (UFH), yet may produce life threatening side effects such as systemic hypotension, catastrophic pulmonary vasoconstriction or allergic reactions. We have described 40 kDa dextrans (Dex40) substituted with glycidyltrimethylammonium chloride (GTMAC) as effective, immunogenically and hemodynamically neutral inhibitors of UFH. The aim of the present study was to evaluate in mice and rats toxicokinetic profile of the most promising polymer – Dex40-GTMAC3. Polymer was rapidly eliminated with a half-time of 12.5±3.0 min in Wistar rats, and was mainly distributed to the kidneys and liver in mice. The safety studies included the measurement of blood count and blood biochemistry, erythrocyte osmotic fragility and the evaluation of the histological alterations in kidneys, liver and lungs of mice and rats in acute and chronic experiments. We found that Dex40-GTMAC3 is not only effective but also very well tolerated. Additionally, we found that protamine may cause overt hemolysis with appearance of permanent changes in the liver and kidneys. In summary, fast renal clearance behavior and generally low tissue accumulation of Dex40-GTMAC3 is likely to contribute to its superior to protamine biocompatibility. Intravenous administration of therapeutic doses to living animals does not result in the immunogenic, hemodynamic, blood and organ toxicity. Dex40-GTMAC3 seems to be a promising effective and safe candidate for further clinical development as new UFH reversal agent